Punch biopsy, a standard diagnostic procedure for patients with cutaneous lupus erythematosus (CLE) carries an infection risk, is invasive, uncomfortable and potentially scarring, and impedes patient recruitment in clinical trials. Non-invasive tape sampling is an alternative that could enable serial evaluation of specific lesions. This cross-sectional pilot research study evaluated the use of a non-invasive adhesive tape device to collect messenger RNA (mRNA) from the skin surface of participants with CLE and healthy volunteers (HVs) and investigated its feasibility to detect biologically meaningful differences between samples collected from participants with CLE and samples from HVs.
Affected and unaffected skin tape samples and simultaneous punch biopsies were collected from 10 participants with CLE. Unaffected skin tape and punch biopsies were collected from 10 HVs. Paired samples were tested using quantitative PCR for a candidate immune gene panel and semi-quantitative immunohistochemistry for hallma throughout a clinical trial.
A non-invasive tape RNA collection technique is a potential tool for repeated skin biomarker measures throughout a clinical trial.Improvements in maternal and infant health outcomes are policy priorities in Kenya. Achieving these outcomes depends on early identification of pregnancy and quality of primary healthcare. Quality improvement interventions have been shown to contribute to increases in identification, referral and follow-up of pregnant women by community health workers. In this study, we evaluate the cost-effectiveness of using quality improvement at community level to reduce maternal and infant mortality in Kenya.
We estimated the cost-effectiveness of quality improvement compared with standard of care treatment for antenatal and delivering mothers using a decision tree model and taking a health system perspective. We used both process (antenatal initiation in first trimester and skilled delivery) and health outcomes (maternal and infant deaths averted, as well as disability-adjusted life years (DALYs)) as our effectiveness measures and actual implementation costs, discounting costs only. We conducted deterministic and prctive compared with the standard community healthcare in Kenya due to improvements in antenatal care uptake and skilled delivery. It is likely that quality improvement interventions are a good investment and may also yield benefits in other health areas.Specific mechanisms by which tumor-infiltrating lymphocytes (TIL) become dysfunctional remain poorly understood. Here, we employed a two-pronged approach using single-cell mass cytometry and tissue imaging technologies to dissect TILs from 25 patients with resectable and 35 patients with advanced non-small cell lung cancer (NSCLC). We identified a burned-out CD8+ TIL subset (Ebo) that specifically accumulated within the tumor microenvironment (TME) but not in adjacent nontumoral tissues. Ebo showed the highest expression of proliferation and activation markers but produced the lowest amount of IFNγ and were the most apoptotic CD8+ TIL subset. Using a humanized patient-derived tumor xenograft model, we demonstrated that Ebo expansion occurred within the TME in a PD-1/B7-H1 pathway-dependent manner. Ebo abundance in baseline tumor tissues was associated with resistance to anti-PD therapy in patients with NSCLC. Our study identifies a dysfunctional TIL subset, with distinct features from previously described exhausted T cells, and implies strategies to overcome immunotherapy resistance. SIGNIFICANCE We identified a highly proliferative, overactivated, and apoptotic dysfunctional CD8+ tumor-infiltrating subpopulation that is functionally distinct from previously described exhausted T cells. This population is expanded in lung cancer tissues in a PD-1/B7-H1-dependent manner, and its abundance is associated with resistance to cancer immunotherapy, thus becoming a potential tissue biomarker.This article is highlighted in the In This Issue feature, p. 1601.There is potential for fecal microbiome profiling to improve colorectal cancer screening. This has been demonstrated by research studies, but it has not been quantified at scale using samples collected and processed routinely by a national screening program.
Between 2016 and 2019, the largest of the NHS Bowel Cancer Screening Programme hubs prospectively collected processed guaiac fecal occult blood test (gFOBT) samples with subsequent colonoscopy outcomes blood-negative [= 491 (22%)]; colorectal cancer [= 430 (19%)]; adenoma [= 665 (30%)]; colonoscopy-normal [= 300 (13%)]; nonneoplastic [= 366 (16%)]. Samples were transported and stored at room temperature. DNA underwent 16S rRNA gene V4 amplicon sequencing. Taxonomic profiling was performed to provide features for classification via random forests (RF).
Samples provided 16S amplicon-based microbial profiles, which confirmed previously described colorectal cancer-microbiome associations. Microbiome-based RF models showed potential as a fd routinely by a national colorectal cancer screening program to improve accuracy as a first- or second-tier screen. The models required as few as 15 taxa, raising the potential of an inexpensive qPCR test. This could reduce the number of colonoscopies in countries that use fecal occult blood test screening.Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare, aggressive form of RCC associated with hereditary leiomyomatosis and RCC syndrome. Evidence for systemic therapy efficacy is lacking.
We studied clinical and genomic characteristics of FH-RCC, including response [objective response rate (ORR)] to systemic therapies and next-generation sequencing (NGS). Patients with metastatic FH-RCC, defined by presence of pathogenic germline or somatic mutation plus IHC evidence of FH loss, were included.
A total of 28 of 32 included patients (median age 46; range, 20-74; MF, 2012) underwent germline testing; 23 (82%) harbored a pathogenic germline variant. Five (16%) were negative for germline mutations; all had biallelic somatic loss. https://www.selleckchem.com/products/gcn2-in-1.html Somatic NGS (31/32 patients) revealed co-occurring mutation most frequently (= 5). Compared with clear-cell RCC, FH-RCC had a lower mutation count (median 2 vs. 4; &lt; 0.001) but higher fraction of genome altered (18.7% vs. 10.3%; = 0.001). A total of 26 patients were evaluable for response to systemic therapy mTOR/VEGF combination (= 18, ORR 44%), VEGF monotherapy (= 15, ORR 20%), checkpoint inhibitor therapy (= 8, ORR 0%), and mTOR monotherapy (= 4, ORR 0%).